The Structural Biology Shared Resource provides state-of-the-art infrastructure and expertise needed for high quality protein production and high resolution structure determination by NMR and X-ray crystallography. These capabilities are complemented by significant strengths in cryo-electron microscopy, electron paramagnetic resonance, a wide range of vibrational spectroscopies, computational biology and unique macromolecular foot printing approaches at the College and AECC. Through the New York Structural Genomics Research Consortium (NYSGRC), AECC investigators have access to -25-30 shifts (8 hour blocks) on the X29 insertion device at the National Synchrotron Light Source (NSLS), Brookhaven National Laboratory, as well as outstanding access to the LRL-CAT beamline (administered by Eli Lilly & Co.) at the Advanced Photon Source (APS), which provides FEDEX crystallographic service at one of the premiere beamlines in the world. Moreover, through membership in the New York Structural Biology Center, AECC investigators have access to the X4A bending magnet beamline at NSLS. These arrangements ensure that access to data collection resources is never rate limiting. There is also in-house Rigaku rotating anode/image plate data collection capabilities essential for characterization and screening of samples prior to synchrotron analysis. NMR capabilities at Einstein consists of one 300 MHz and two 600 MHz NMR spectrometers, with a cryoprobe on one of the 600s. AECC investigators also have full access to the NYSBC making available two 900 MHz and three 800 MHz instruments, all with cryoprobes, and one 750 MHz solid state NMR spectrometer. As proposed in the previous application, the Structural Biology Shared Resource has established unique capabilities, including considerable automation and expertise, which support large-scale and high-throughput protein production in E. coli, insect cell and mammalian expression platforms. Additional automation supports high-throughput protein crystallization and crystal imaging. The Facility is now working to implement modest fragment-based screening capabilities to leverage the numerous proteins and structures being produced, and is positioned to exploit NSLS-II, the new third generation synchrotron facility being constructed at Brookhaven National Laboratory. Together, these capabilities provide the AECC community with a powerful infrastructure that will make it possible to realize protein reagents and structural information to drive a wide range of biology and therapeutics.